2-Mercapto-1,3,4-thiadiazole-functionalized gold nanoclusters as a comparable bactericidal nanoantibiotic to vancomycin in treating methicillin-resistant Staphylococcus aureus infections

In recent decades, methicillin-resistant Staphylococcus aureus (MRSA) has emerged, disseminated globally, and become a leading cause of bacterial infections. Although gold nanoclusters have been widely studied as novel antimicrobial agents, the design idea of high antibacterial activities of gold nanoclusters modified by ligands is still unclear. In addition, their main antibacterial mechanism is considered as the production of reactive oxygen species, and thus, it is hard to achieve outstanding bactericidal activity via a single pathway. Therefore, the search for novel gold nanoclusters with higher antimicrobial activity for treating MRSA infections continues. In this study, we developed 2-mercapto-1,3,4-thiadiazole (MTD)-functionalized gold nanoclusters (AuNCs) that show comparable bactericidal activity to vancomycin towards MRSA. Moreover, we found that the MTD-AuNCs could down regulate of the expression of the bacterial Na+/H+ antiporter, which may lead to the accumulation of Na+ intracellular and further influence the cell volume. In addition, the influx of H+ may also be impeded, followed by the reduce of adenosine triphosphate synthesis, resulting in cell death. Furthermore, satisfactory biocompatibility and no cytotoxicity toward mammalian erythrocytes or cells was observed. The AuNCs also significantly decreased inflammatory responses and accelerated the healing of MRSA-induced wounds in a rat model. The use of ligands such as MTD could inspire the design of other gold nanoclusters as novel nanoantibiotics in treating MRSA infections.